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Class: Dihydropyridines
- Calcium-Channel Blocking Agents, Dihydropyridine
- Dihydropyridine Calcium-Channel Blocking Agents
- Calcium Antagonists
VA Class: CV200
CAS Number: 54527-84-3
Brands: Cardene

Medically reviewed by Last updated on Apr 8, 2019.


Calcium-channel blocking agent; dihydropyridine derivative.1

Uses for Nicardipine


Oral management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 500

Therapy with extended-release capsules generally is preferred because of less frequent dosing, potentially smoother BP control,500 and concerns raised by experience with short-acting (conventional, immediate-release) nifedipine.35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 61 72 73

Calcium-channel blockers are recommended as one of several preferred agents for the initial management of hypertension; other options include ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 503 504 Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).500 501 502 503 504 515

Calcium-channel blockers may be preferred in hypertensive patients with certain coexisting conditions (e.g., ischemic heart disease)523 and in geriatric patients, including those with isolated systolic hypertension.502 510

Black hypertensive patients generally respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists).500 501 504 However, diminished response to these other drug classes is largely eliminated when administered concomitantly with a calcium-channel blocker or thiazide diuretic.500 504

The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530

JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515

In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541

IV, short-term management of hypertension when oral therapy is not feasible or desirable.18

IV management of hypertensive crises (e.g., emergencies) in adults.18 500

IV, rapid reduction of BP in the management of severe hypertension in pediatric patients 1–17 years of age.99


Management of chronic stable angina pectoris (alone or in combination with other antianginal agents).1 3 25

Nicardipine Dosage and Administration


BP Monitoring and Treatment Goals

  • Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

  • When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

  • If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501

  • Consider initiating antihypertensive therapy with a combination of drugs if patient's BP exceeds goal BP by >20/10 mm Hg.500 501 503 504

  • Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)


Administer orally1 2 5 or by IV infusion.18 22 23

Oral Administration

Conventional Capsules

Administer orally 3 times daily.1

Extended-release Capsules

Administer orally twice daily.2

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by slow, continuous IV infusion.18 22 23

Must dilute commercially available injection concentrate containing 2.5 mg/mL with a compatible IV infusion solution prior to administration.18

Alternatively, administer as premixed solution (0.1 mg/mL in either 4.8% dextrose or 0.86% sodium chloride injection, 0.2 mg/mL in either 5% dextrose or 0.83% sodium chloride injection).600 601

If administered via a peripheral vein, change infusion site every 12 hours to minimize risk of venous irritation.18

Monitor BP closely during and after completion of IV administration; avoid rapid or excessive reduction in systolic or diastolic BP.18


Injection concentrate: Dilute each 25-mg ampul containing 2.5 mg/mL with 240 mL of a compatible IV solution (see Solution Compatibility under Stability) to provide a solution containing 0.1 mg/mL.18 c


Available as nicardipine hydrochloride; dosage is expressed in terms of the salt.a b c

Pediatric Patients

Severe Hypertension
Rapid Reduction of BP

Children and adolescents 1–17 years of age: 1–3 mcg/kg per minute as infusion.99


Conventional Capsules

Initially, 20 mg 3 times daily.1 5

Adjust dosage according to patient’s peak (approximately 1–2 hours after dosing, particularly during initiation of therapy) and trough (8 hours after dosing) BP responses, but generally no more frequently than at 3-day intervals.1

Usual dosage is 20–40 mg 3 times daily.1

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Extended-Release Capsules

Initially, 30 mg twice daily.2 70

Adjust dosage according to BP response 2–4 hours after dosing as well as just prior to next dose.2

Usual dosage range is 30–60 mg twice daily.2 500

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Switching to Extended-Release Capsules

Total daily dose of conventional tablets not a useful guide to judging effective dose of extended-release capsules.2 c However, may administer the currently effective total daily dose of conventional capsules and adjust dosage according to BP response.2 c

Short-term Management with IV Therapy

Initially, 5 mg/hour.18 70

If target BP is not achieved, increase rate by 2.5 mg/hour every 15 minutes, up to 15 mg/hour.18 70

For more rapid reduction, initially, 5 mg/hour. If the target BP is not achieved, increase rate by 2.5 mg/hour every 5 minutes, up to 15 mg/hour.18 70

Following achievement of desired BP response, decrease rate to 3 mg/hour;18 adjust rate as necessary to maintain desired BP response.18

Conversion From Oral to IV Therapy
Recommended Infusion Rates for Patients Previously Maintained on Oral Therapy.

Oral Dosage (as Conventional Capsules)

Equivalent IV Infusion Rates

20 mg every 8 hours

0.5 mg/hour

30 mg every 8 hours

1.2 mg/hour

40 mg every 8 hours

2.2 mg/hour

Hypertensive Emergency

5–15 mg/hour; adjust according to BP response and tolerance.500

Initially, reduce mean arterial BP by no more than 25% within minutes to 1 hour, then further reduce if stable toward 160/100 to 110 mm Hg within the next 2–6 hours, avoiding excessive declines in pressure that could precipitate renal, cerebral, or coronary ischemia.500

If patient is stable, can further reduce BP toward normal in the next 24–48 hours.500

Conventional Capsules

Initially, 20 mg 3 times daily.1 5 Adjust dosage according to patient tolerance and response at ≥3-day intervals.1

Usual dosage range is 20–40 mg 3 times daily.1

Prescribing Limits



15 mg/hour.18

Special Populations

Hepatic Impairment

Conventional capsules: Initially, 20 mg twice daily in patients with severe hepatic impairment.1 Individualize dosage, but maintain a twice-daily dosing schedule.1

IV infusion: Consider dosage reduction.18 Use with caution in patients with portal hypertension.18

Renal Impairment

Conventional capsules: Initially, 20 mg 3 times daily.1 5 Titrate dosage carefully.1

Extended-release capsules: Initially, 30 mg twice daily.2 Titrate dosage carefully.2

IV infusion: Titrate dosage carefully.18

Geriatric Patients

Cautious dosing recommended.a b For conventional and extended-release capsules, initiate therapy at low end of dosage range.20 68

Cautions for Nicardipine


  • Known hypersensitivity to nicardipine or any ingredient in the formulation.1 2 18

  • Advanced aortic stenosis, since reduction in diastolic pressure may worsen myocardial oxygen balance.1 2 18



Increased Angina

Increased frequency, duration, and severity of angina upon initiation or dosage increase of calcium channel blockers.1 2 18

Heart Failure

Use with caution in patients with heart failure or substantial left ventricular dysfunction, especially in those receiving concomitant β-adrenergic blocking agents.1 2 18

β-Blocker Withdrawal

Taper dosage of β-adrenergic blocking agent, preferably over 8–10 days before initiation of nicardipine.1 2 18 Nicardipine is not a β-adrenergic blocking agent and offers no protection against abrupt withdrawal of these agents.1 2 18

General Precautions


Possible symptomatic hypotension from decreased peripheral resistance.1 2 18 Use with caution in patients with acute cerebral infarction or hemorrhage; avoid systemic hypotension in these patients.1 2 18

Monitor BP carefully, especially during initiation of therapy or upward adjustment of dosage.1


Limited clinical experience in patients with hypertension associated with pheochromocytoma.18 Use with caution.18

Specific Populations


Category C.1 2 18


Distributed into milk in high concentrations in rats.1 2 18 Use not recommended.1 2 18

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 2 18

Use with caution for rapid reduction of BP in pediatric patients 1–17 years of age; may cause reflex tachycardia.99

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.a b Select dosage with caution; initiate dosage at lower end of recommended range.a b

Hepatic Impairment

Use with caution in patients with hepatic impairment or reduced hepatic blood flow; dosage adjustments recommended.1 2 18 24 (See Hepatic Impairment under Dosage and Administration.)

Use of extended-release capsules has not been studied in patients with severe hepatic impairment.2

Renal Impairment

Use with caution; careful dosage titration recommended.1 2 18 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

With oral therapy, pedal edema, dizziness, headache, asthenia, flushing, increased angina, vasodilation, palpitation.a b

With IV therapy, headache, hypotension, nausea/vomiting, tachycardia.c

Interactions for Nicardipine

Specific Drugs




Antacids (magnesium hydroxide)

Pharmacokinetic interaction unlikely1 2 18

β-Adrenergic blockers (e.g., propranolol)

Pharmacokinetic interaction (e.g., effect on plasma protein binding of nicardipine) unlikely1 2 18


Increased plasma nicardipine concentrations1 2 18

Monitor carefully1 2 18


Increased plasma cyclosporine concentrations1 2 18

Monitor plasma cyclosporine concentrations closely and adjust dosage accordingly1 2 18


Potential for increased plasma digoxin concentrations1 2 18

Monitor serum digoxin concentrations1 2 18


No effect on plasma protein binding of nicardipine1 2 18


Potential for severe hypotension with concomitant use of a β-adrenergic blocker and a calcium channel blocker1 2 18

Increase circulating fluid volume if hypotension occurs1 2 18


No effect on plasma protein binding of nicardipine1 2 18


No effect on plasma protein binding of nicardipine1 2 18


No effect on plasma protein binding of nicardipine1 2 18


No effect on plasma protein binding of nicardipine1 2 18

Nicardipine Pharmacokinetics



Completely absorbed from the GI tract following oral administration; peak plasma concentrations of conventional and extended-release capsules are attained within 0.5–2 and 1–4 hours, respectively.1 2

Minimum plasma levels of equivalent doses of conventional and extended-release capsules are similar.2

Bioavailability of conventional capsules is about 35%;1 2 extended-release capsules have a slightly lower bioavailability, except at the highest doses.2


High-fat meal decreases bioavailability of conventional and extended-release capsules.1 2

Special Populations

In patients with severe hepatic impairment, peak plasma concentrations and AUC increased by 1.8 and 4-fold, respectively, and terminal half-life prolonged to 19 hours.1 2

In patients with moderate renal impairment, peak plasma concentrations and AUC increased by 2- to 3-fold following administration of conventional or extended-release capsules.1 2



Distributed into milk in rats.1 2

Plasma Protein Binding

>95%.1 2 18



Extensively metabolized in the liver.1 2 18

Elimination Route

Excreted in urine (49–60%) and feces (35–43%).1 2 18


Multi-phasic; terminal elimination half-life is 8.6 and 14.4 hours following oral and IV administration, respectively.1 2 18




Conventional Capsules and Extended-release Capsules

Light resistant containers at 15–30°C.a b


Injection Concentrate

20–25°C; protect from light.c Avoid exposure to increased temperatures.c

Premixed Injection for Infusion

20–25°C; protect from light, freezing, and excessive heat.600 601


For information on systemic interactions resulting from concomitant use, see Interactions.


Solution CompatibilityHID


Dextrose 5% in sodium chloride 0.45% or 0.9%

Dextrose 5% in water with potassium chloride 0.3%

Sodium chloride 0.9%


Sodium bicarbonate 5%


Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.45%

Drug CompatibilityHID
Admixture Compatibility


Potassium chloride

Y-Site CompatibilityHID


Amikacin sulfate



Butorphanol tartrate

Calcium gluconate

Cefazolin sodium

Chloramphenicol sodium succinate

Clindamycin phosphate


Dextran 40 in dextrose 5%

Diltiazem HCl

Dobutamine HCl

Dopamine HCl


Epinephrine HCl

Erythromycin lactobionate

Esmolol HCl


Fenoldopam mesylate

Fentanyl citrate

Gentamicin sulfate

Hetastarch in sodium chloride 0.9%

Hydrocortisone sodium succinate

Hydromorphone HCl

Labetalol HCl

Lidocaine HCl



Magnesium sulfate

Methylprednisolone sodium succinate


Midazolam HCl

Milrinone lactate

Morphine sulfate

Nafcillin sodium



Norepinephrine bitartrate

Penicillin G potassium

Potassium chloride

Potassium phosphates

Ranitidine HCl

Sodium acetate

Sodium nitroprusside

Tobramycin sulfate

Vancomycin HCl

Vecuronium bromide


Ampicillin sodium

Ampicillin sodium-sulbactam sodium

Cefepime HCI


Micafungin sodium



Heparin sodium


  • Inhibits transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations.a b c

  • Peripheral arterial vasodilator; acts directly on vascular smooth muscle causing reduction in peripheral vascular resistance (afterload) and BP.a b c

Advice to Patients

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 2 18

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 18

  • Importance of informing patients of other important precautionary information.1 2 18 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

niCARdipine Hydrochloride


Dosage Forms


Brand Names




20 mg*

Nicardipine Hydrochloride Capsules

30 mg*

Nicardipine Hydrochloride Capsules

Capsules, extended-release

30 mg

Cardene SR


60 mg

Cardene SR


For injection, concentrate, for IV infusion

2.5 mg/mL*

Cardene I.V.


Nicardipine Hydrochloride Injection

niCARdipine Hydrochloride in Dextrose


Dosage Forms


Brand Names



Injection, for IV infusion

0.1 mg/mL (20 mg) in 4.8% Dextrose

Cardene I.V.


0.2 mg/mL (40 mg) in 5% Dextrose

Cardene I.V.


niCARdipine Hydrochloride in Sodium Chloride


Dosage Forms


Brand Names



Injection, for IV infusion

0.1 mg/mL (20 mg) in 0.86% Sodium Chloride

Cardene I.V.


0.2 mg/mL (40 mg) in 0.83% Sodium Chloride

Cardene I.V.


AHFS DI Essentials™. © Copyright 2019, Selected Revisions November 17, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


1. Syntex Laboratories, Inc. Cardene (nicardipine hydrochloride) capsules prescribing information. Palo Alto CA; 1992 Jul.

2. Syntex Laboratories, Inc. Cardene SR (nicardipine hydrochloride) sustained release capsules prescribing information. Palo Alto CA; 1992 Jan.

3. Freedman DD, Waters DD. Second generation dihydropyridine calcium antagonists. Greater vascular selectivity and some unique applications. Drugs. 1987; 34:578-98.

4. Murdoch D, Heel RC. Amlodipine : a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in cardiovascular disease. Drugs. 1991; 41:478-505.

5. Sorkin EM, Clissold SP. Nicardipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in the treatment of angina pectoris, hypertension and related cardiovascular disorders. Drugs. 1987; 33:296-345.

8. Syntex Laboratories, Inc, Palo Alto, CA: (personal observations).

9. Sandoz Pharmaceuticals Corp. DynaCirc (isradipine) capsules prescribing information. East Hanover, NJ; 1992 Jun.

10. Lopez LM, Santiago TM. Isradipine—another calcium-channel blocker for the treatment of hypertension and angina. Ann Pharmacother. 1992; 26:789-99.

11. Fitton A, Benfield P. Isradipine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cardiovascular disease. Drugs. 1990; 40:31-74.

12. Walton T, Symes LR. Felodipine and isradipine: new calcium-channel blocking agents for the treatment of hypertension. Clin Pharm. 1993; 12:261-75.

14. Prisant LM, Carr AA, Nelson EB et al. Isradipine vs propranolol in hydrochlorothiazide-treated hypertensives: a multicenter evaluation. Arch Intern Med. 1989; 149:2453-7.

15. Anon. Isradipine for hypertension. Med Lett Drugs Ther. 1991; 33:51-4.

16. Alderman MH. Which antihypertensive drugs first—and why! JAMA. 1992; 267:2786-7. Editorial.

17. Weber MA, Laragh JH. Hypertension: steps forward and steps backward: the Joint National Committee fifth report. Arch Intern Med. 1993; 153:149-52.

18. PDL Biopharma. Cardene I.V. (nicardipine hydrochloride) prescribing information. Philadelphia PA; 2006 Jan.

19. Fagan TC, Tyler ED, Reitman MA et al. Sustained-release nicardipine in mild-to-moderate hypertension. Chest. 1993; 104:427-33.

20. Frampton JE, Faulds D. Nicardipine. A review of its pharmacology and therapeutic efficacy in older patients. Drugs Aging. 1993; 3:165-87.

21. Bosch X, Sobrino J, Lopez-Soto A et al. Parotitis due to nicardipine. BMJ. 1992; 304:882.

22. IV Nicardipine Study Group. Efficacy and safety of intravenous nicardipine in the control of postoperative hypertension. Chest. 1991; 99:393-8.

23. Wallin JD, Fletcher E, Ram VS et al. Intravenous nicardipine for the treatment of severe hypertension. A double-blind, placebo-controlled multicenter trial. Arch Intern Med. 1989; 149:2662-9.

24. Razak TA, McNeil JJ, Sewel RB et al. The effect of hepatic cirrhosis on the pharmacokinetics and blood pressure response to nicardipine. Clin Pharmacol Ther. 1990; 47:463-9.

25. Sklar J, Dennish GW III, Glode J et al. Usefulness of nicardipine as monotherapy for chronic, stable angina. Am J Cardiol. 1989; 63:1203-7.

26. Eicher JC, Chalopin JM, Tanter Y et al. Nicardipine and urinary retention. JAMA. 1987; 258:3388.

27. Dubois C, Blanchard D. Efficacy and safety of nicardipine in 29,104 patients with hypertension. Clin Ther. 1989; 11:452-60.

28. Nami R, Caruso D, Dormi A et al. Efficacy and tolerability of nicardipine slow release and enalapril in elderly hypertensive patients: results of a multicenter study. Curr Ther Res. 1993; 54:221-31.

29. Kubota K, Pearce GL, Inman WHW. Vasodilation-related adverse events in diltiazem and dihydropyridine calcium antagonists studied by prescription-event monitoring. Eur J Clin Pharmacol. 1995; 48:1-7.

30. Jannet D, Carbonne B, Sebban E et al. Nicardipine versus metoprolol in the treatment of hypertension during pregnancy: a randomized comparative trial. Obstet Gynecol. 1994; 84:354-9.

31. Carbonne B, Jannet D, Touboul C et al. Nicardipine treatment of hypertension during pregnancy. Obstet Gynecol. 1993; 81:908-14.

32. Narváez M, Figueras A, Capellá D et al. Tinnitus with calcium-channel blockers. Lancet. 1994; 343:1229-30.

33. Agre K. An overview of the safety and efficacy of nicardipine in clinical trials. Am J Cardiol. 1987; 59:31J-5J.

34. Ahmad S. Nicardipine-induced hyperglycemia. Am Fam Physician. 1992; 45:449,452.

35. Glasser SP, Clark PI, Lipicky RJ et al. Exposing patients with chronic, stable, exertional angina to placebo periods in drug trials. JAMA. 1991; 265:1550- 4.

36. National Heart, Lung, and Blood Institute. NHLBI panel reviews safety of calcium channel blockers. Rockville, MD; 1995 Aug 31. Press release.

37. National Heart, Lung, and Blood Institute. New analysis regarding the safety of calcium-channel blockers: a statement for health professionals from the National Heart, Lung, and Blood Institute. Rockville, MD; 1995 Sep 1.

38. Anon. NHLBI panel stands by JNC V in response to Circulation CCB article; AIM report supports use of beta blockers for prevention of sudden cardiac death. F-D-C Rep. 1995; 57(Sep 4):3-4.

39. American Heart Association. Public advisory statement on calcium channel blocker drugs. Dallas, TX; 1995 Aug 28.

40. Psaty BM, Heckbert SR, Koepsell TD et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA. 1995; 274:620-5.

41. Psaty BM, Heckbert SR, Koepsell TD et al. The risk of incident myocardial infarction associated with anti- hypertensive drug therapies. Circulation. 1995; 91:925.

42. Buring JE, Glynn RJ, Hennekens CH. Calcium channel blockers and myocardial infarction: a hypothesis formulated but not yet tested. JAMA. 1995; 274:654-5.

43. Furberg CD, Psaty BM, Meyer JV. Nifedipine: dose-related increase in mortality in patients with coronary heart disease. Circulation. 1995; 92:1326-31.

44. Opie LH, Messerli FH. Nifedipine and mortality: grave defects in the dossier. Circulation. 1995; 92:1068-73.

45. Kloner RA. Nifedipine in ischemic heart disease. Circulation. 1995; 92:1074-8.

46. Yusuf S. Calcium antagonists in coronary artery disease and hypertension: time for reevaluation? Circulation. 1995; 92:1079-82. Editorial.

47. Lenfant C. The calcium channel blocker scare: lessons for the future. Circulation. 1995; 91:2855-6.

48. Habib GB. Are calcium antagonists harmful in hypertensive patients? Distinguishing hype from reality. Chest. 1995; 108:3-5.

49. Horton R. Spinning the risks and benefits of calcium antagonists. Lancet. 1995; 346:586-7.

50. Yusuf S, Held P, Furberg C. Update of effects of calcium antagonists in myocardial infarction or angina in light of the Second Danish Verapamil Infarction Trial (DAVIT-II) and other recent studies. Am J Cardiol. 1991; 67:1295-7.

51. Egstrup K, Andersen PE Jr. Transient myocardial ischemia during nifedipine therapy in stable angina pectoris, and its relation to coronary collateral flow and comparison with metoprolol. Am J Cardiol. 1993; 71:177-83.

52. Wagenknecht LE, Furberg CD, Hammon JW et al. Surgical bleeding: unexpected effect of a calcium antagonist. BMJ. 1995; 310:776-7.

53. Miles Inc. American Heart Association, Dr. Psalty and Miles Inc. release statements qualifying possible risks of calcium channel blockers. West Haven, CT; 1995 Mar 15. Press release.

54. Dear healthcare professional letter regarding calcium-channel blockers and increased risk of heart attack. Chicago:Searle. 1995 Mar 17.

55. McClellan K. Unexpected results from MIDAS in atherosclerosis. Inpharma Wkly. 1994; Apr 9:4.

56. Anon. Groups act to dispel concerns about calcium-channel blockers. Am J Health- Syst Pharm. 1995; 52:1154,1158.

57. Waters D. Proischemic complications of dihydropyridine calcium channel blockers. Circulation. 1991; 84:2598-600.

58. Messerli FH. Case-control study, meta-analysis, and bouillabaisse: putting the calcium antagonist scare into context. Ann Intern Med. 1995; 123:888-9.

59. Reviewers’ comments (personal observations).

60. Pratt Pharmacueticals. Procardia (nifedipine) capsules prescribing information (dated 1993 Feb). In: Physicians’ desk reference. 49th ed. Montvale, NJ: Medical Economics Company Inc; 1995:1906-7.

61. Held PH, Yusuf S, Furberg CD. Calcium channel blockers in acute myocardial infarction and unstable angina: an overview. BMJ. 1989; 299:1187-92.

62. Kitler ME. The changing face of hypertension and antihypertensive agents. Drugs Aging. 1996; 8:5-11.

63. Parker BM, Cusack BJ, Vestal RE. Pharmacokinetic optimisation of drug therapy in elderly patients. Drugs Aging. 1995; 7:10-8.

64. Kvasnicka J, Flack JM, Grimm RH. Treatment of hypertension in the presence of coexisting medical conditions. Drugs Aging. 1994; 4:304-12.

65. Kelly JG, O’Malley K. Calcium antagonists in the elderly. Drugs Aging. 1993; 3:400-7.

66. Burris JF. Practical considerations in treating the elderly hypertensive patient. Am J Med. 1991; 90(Suppl 4B):28-31S.

67. O’Malley K, Cox JP, O’Brien E. Choice of drug treatment for elderly hypertensive patients. Am J Med. 1991; 90(Suppl 3A):27-33S.

68. Food and Drug Administration. Specific requirements on content and format of labeling for human prescrption drugs; proposed addition of ”geriatric use“ subsection in the labeling; proposed rule (Docket No. 89N-0474). Fed Regist. 1990; 55:46134-7.

69. Bailey DG, Arnold JMO, Spence JD. Grapefruit juice and drugs: how significant in the interaction? Clin Pharmcokinet. 1994; 26:91-8.

70. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)

71. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80.

72. Psaty BM, Smith NL, Siscovich DS et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA. 1997; 277:739-45.

73. American College of Cardiology and American Heart Association. ACC/AHA guidelines for the management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol. 1996; 28:1328-428.

75. Velussi M, Brocco E, Frigato F et al. Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients. Diabetes. 1996; 45:216-22.

76. Estacio RO, Jeffers BW, Hiatt WR et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med. 1998; 338:645-52.

77. Pahor M, Psaty BM, Furberg CD. Treatment of hypertensive patients with diabetes. Lancet. 1998; 351:689-90.

78. Tatti P, Pahor M, Byington RP et al. Outcome results of the Fosinopril versus Amlodipine Cardiovascular Events randomized Trial (FACET) in patients

79. Byington RP, Craven TE, Furberg CD et al. Isradipine, raised glycosylated haemoglobin, and risk of cardiovascular events. Lancet. 1997; 350:1075-6.

80. Alderman M, Madhavan S, Cohen H. Calcium antagonists and cardiovascular events in patients with hypertension and diabetes. Lancet. 1998; 351:216-7.

81. Josefson D. Infarction risk found with calcium channel blocker. BMJ. 1998; 316:797.

82. Cutler JA. Calcium-channel blockers for hypertension—uncertainty continues. N Engl J Med. 1998; 338:679-81.

83. Bayer, West Haven, CT: Personal communication.

84. Bakris GL, Copley JB, Vicknair N et al. Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney Int. 1996; 50:1641-50.

85. Ameer B, Weintraub RA. Drug interactions with grapefruit juice. Clin Phramacokinet. 1997; 33:103-21.

86. Roller L. Drugs and grapefruit juice. Clin Pharmacol Ther. 1998; 63:87.

87. Spence JD. Drugs and grapefruit juice. Clin Pharmacol Ther. 1998; 63:87-8.

88. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4.

89. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20.

90. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61.

91. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site.

92. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60.

93. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-riskhypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97.

96. Kaplan NM. The meaning of ALLHAT. J Hypertens. 2003; 21:233-4.

99. National high blood pressure education program working group on hypertension control in children and adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114(Suppl 2):555-76.

100. Wright JT, Dunn JK, Cutler JA et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. 2005; 293:1595-607.

101. Neaton JD, Kuller LH. Diuretics are color blind. JAMA. 2005; 293:1663-6.

102. Leenen FHH, Nwachuku CE, Black HR et al. Clinical events in high-risk hypertensive patients randomly assigned to calcium-channel blocker versus angiotensin-converting enzyme inhibitor in the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial. Hypertension. 2006; 48:374-84.

103. Messerli FH, Staessen JA. Amlodipine better than lisinopril: how one randomized clinical trial ended fallacies from observational studies? Hypertension. 2006; 48:359-61. Editorial.

500. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Bethesda, MD: National Institutes of Health; 2004 Aug. (NIH publication No. 04-5230.)

501. James PA, Oparil S, Carter BL et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311:507-20.

502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281-357.

503. Go AS, Bauman MA, Coleman King SM et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014; 63:878-85.

504. Weber MA, Schiffrin EL, White WB et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014; 16:14-26.

505. Wright JT, Fine LJ, Lackland DT et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014; 160:499-503.

506. Mitka M. Groups spar over new hypertension guidelines. JAMA. 2014; 311:663-4.

507. Peterson ED, Gaziano JM, Greenland P. Recommendations for treating hypertension: what are the right goals and purposes?. JAMA. 2014; 311:474-6.

508. Bauchner H, Fontanarosa PB, Golub RM. Updated guidelines for management of high blood pressure: recommendations, review, and responsibility. JAMA. 2014; 311:477-8.

510. Staessen JA, Fagard R, Thijs L et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997; 350:757-64.

511. JATOS Study Group. Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res. 2008; 31:2115-27.

515. Thomas G, Shishehbor M, Brill D et al. New hypertension guidelines: one size fits most?. Cleve Clin J Med. 2014; 81:178-88.

516. Wright JT, Bakris G, Greene T et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002; 288:2421-31.

520. American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014; 37 Suppl 1:S14-80.

522. Patel A, ADVANCE Collaborative Group, MacMahon S et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007; 370:829-40.

523. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471.

524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240-327.

525. Smith SC, Benjamin EJ, Bonow RO et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011; 124:2458-73.

526. Kernan WN, Ovbiagele B, Black HR et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014; :.

527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 127:e362-425.

530. Myers MG, Tobe SW. A Canadian perspective on the Eighth Joint National Committee (JNC 8) hypertension guidelines. J Clin Hypertens (Greenwich). 2014; 16:246-8.

535. Taler SJ, Agarwal R, Bakris GL et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis. 2013; 62:201-13.

536. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012: 2: 337-414.

541. Perk J, De Backer G, Gohlke H et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012; 33:1635-701.

542. Marik PE, Varon J. Hypertensive crises: challenges and management. Chest. 2007; 131:1949-62.

600. Baxter. Cardene IV Premixed injection (0.1 mg/mL) in either 4.8% dextrose or 0.86% sodium chloride prescribing information. Deerfield, IL; 2013 Jan.

601. Baxter. Cardene IV Premixed injection (0.2 mg/mL) in either 5% dextrose or 0.83% sodium chloride prescribing information. Deerfield, IL; 2013 Jan.

a. Roche Pharmaceuticals. Cardene (nicardipine hydrochloride) capsules prescribing information. Nutley, NJ; 1999 Sep.

b. Roche Pharmaceuticals. Cardene SR (nicardipine hydrochloride) sustained release capsules prescribing information. Nutley, NJ; 2000 Aug.

c. ESP Pharma. Cardene I.V. (nicardipine hydrochloride) prescribing information. Edison, NJ; 2002 Dec.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:849-53.